OBJECTIVES: This study aimed to test potential modifying effects of education on the association between apolipoprotein E epsilon4 (Apo E4) and cognitive decline. METHODS: A community cohort(N=683) aged 65 or over completed the Korean version of Mini-Mental State Examination(MMSE-K) at baseline and two years later(1999-2001). Apo E polymorphisms were genotyped, and classified into that with or without Apo E4. Educational levels were categorized into people with or without education. Covariates included demographic(age, gender), life style(smoking, alcohol drinking), clinical (depression, sleep disorder, vascular risk factors) characteristics. RESULTS: The association between Apo E4 and cognitive decline was significant only in the old persons with no education. The interaction term between education and Apo E4 on cognitive decline was significant (p=0.040). CONCLUSION: Elders with no education might be more vulnerable to the impact of Apo E4 on cognitive decline, which suggests gene-environment interaction.
Aged ; Apolipoprotein E4 ; Apolipoproteins ; Apolipoproteins E ; Gene-Environment Interaction ; Humans

Humans ; Alzheimer Disease/genetics* ; Apolipoprotein E4/genetics* ; Amyloid beta-Peptides

BACKGROUND: The aim of this study was to investigate the association between apo E and ACE genetic polymorphism and diabetic nephropathy. METHODS: One hundred eighteen patients with type 2 diabetes who had a duration of diabetes longer than 8 years were divided into the three apo E groups (E2, E3, E4) and three ACE groups (II, ID, DD). Plasma levels of lipids were measured. The frequency of diabetic nephropathy and clinical and biochemical characteristics were compared among the Apo E and ACE genotype groups. RESULTS: The frequency of overt nephropathy was significantly greater in apo E2 patients with diabetes (46.7%) than apo E3 (16.7%) or apo E4 patients (10.5%). Logistical regression analysis showed that odds ratio of apo E2 and apo E4 genotypes for the presence of overt nephropathy were 4.779 (p<0.01) and 0.643 (p=0.583), respectively. Plasma TG levels were significantly greater in apo E2 patients. This study did not show an association between ACE gene polymorphism and diabetic nephropathy, and no interaction between Apo E and ACE gene polymorphism. CONCLUSION: Apo E2 is a prognostic risk factor for diabetic nephropathy in Korean type 2 diabetes. TG may have an important role of diabetic nephropathy. There were not synergistic effect between Apo E and ACE gene polymorphism in diabetic nephropathy.
Apolipoprotein E2 ; Apolipoprotein E3 ; Apolipoprotein E4 ; Apolipoproteins E ; Apolipoproteins* ; Diabetic Nephropathies ; Genotype ; Humans ; Odds Ratio ; Plasma ; Polymorphism, Genetic* ; Risk Factors

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems

The purpose of this study was to investigate the association among nutrient intakes and health-related lifestyles with cardiovascular disease risk assessed by blood lipid profile according to Apolipoprotein E genotypes. Middle-aged industrial male workers who had completed their annual medical examination were recruited and data of 675 subjects who finished the nutrient survey were used in the analysis. Anthropometric parameters, dietary assessment (FFQ), health-related lifestyles and blood profiles were used for statistical analyses. Apo E genotype groups were classified into the following three genotypes: Apo E2 group (including E2/E2, E2/E3, E2/E4), Apo E3 group (including E3/E3), Apo E4 group (including E3/E4, E4/E4). The frequency of Apo E2, E3, and E4 allele were 13.3%, 75.0% and 11.7% respectively. There were no significant differences in the anthropometric parameters depending on different Apo E genotypes. Also, no significant differences in the nutrient intakes were found according to the genotype groups. The nutrient intakes of all subjects were similar to or higher than the level of KDRIs (Dietary Reference Intakes For Koreans) except for intakes of calcium (67.44% of KDRIs), vitamin A (73.83% of KDRIs) and vitamin B2 (78.02% of KDRIs). Also, there were no significant differences of health-related lifestyles according to Apo E genotype groups. As for the lipid profiles, Apo E4 group had significantly higher total and LDL-cholesterol concentrations than the Apo E2 group (p < 0.05). We confirmed that plasma total and LDL-cholesterol concentrations were greatly influenced by Apo E genotypes. However, nutrient intakes and health-related lifestyles were not associated with Apo E genotypes.
Alleles ; Apolipoprotein E2 ; Apolipoprotein E3 ; Apolipoprotein E4 ; Apolipoproteins ; Apolipoproteins E ; Calcium ; Cardiovascular Diseases ; Genotype ; Humans ; Life Style ; Male ; Plasma ; Riboflavin ; Vitamin A

PURPOSE: Apolipoprotein E (Apo E) plays a major role in lipoprotein metabolism and lipid transport. Many investigators have described that Apo E polymorphisms is one of the most important genetic determinants for cardiovascular disease. The purpose of this study was to evaluate the association between Apo E polymorphisms and serum lipid profiles in obese adolescent. METHODS: We measured the serum concentrations of glucose, apolipoprotein (Apo) A1, Apo B, total cholesterol (TC), triglyceride (TG), HDL and LDL-cholesterol after overnight fasting in obese adolescent. Apo E polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: 86 obese adolescents participated in this study. The body mass index (BMI) of participants were excess of 95 percentile by age and sex. Male to female ratio was 1.7 and mean age of study group was 16.2+/-1.8 years. Mean BMI was 27.4+/-2.5 kg/m2. The frequency of epsilon2, epsilon3 and epsilon4 allele were 8.1%, 87.2% and 4.7% respectively. Study populations were classified into the following three genotypes 1) Apo E2 group (n=13, 15.1%) carrying either the epsilon2/epsilon2 or epsilon2/epsilon3 2) Apo E3 group (n=65, 75.6%) carrying the most frequent epsilon3/epsilon3 3) Apo E4 group (n=8, 9.3%) carrying either the epsilon3/epsilon4 or epsilon4/epsilon4. No differences were found among Apo E genotypes concerning age, sex, weight, height and BMI. Apo B and LDL-cholesterol concentrations were significantly higher in the Apo E4 group (P<0.05). No association were found between Apo E genotypes and glucose, Apo A1, TC, TG and HDL. CONCLUSIONS: We confirmed that serum concentrations Apo B and LDL-cholesterol were influenced by Apo E genotypes. Apo E polymorphisms seems to influence some alteration of lipid metabolism associated with obesity in adolescent.
Adolescent ; Alleles ; Apolipoprotein A-I ; Apolipoprotein E2 ; Apolipoprotein E3 ; Apolipoprotein E4 ; Apolipoproteins ; Apolipoproteins B ; Apolipoproteins E ; Body Mass Index ; Cardiovascular Diseases ; Cholesterol ; Fasting ; Female ; Genotype ; Glucose ; Humans ; Lifting ; Lipid Metabolism ; Lipoproteins ; Male ; Obesity ; Research Personnel

BACKGROUND: Apo E lipoprotein is polymorphic and exists in three common isoforms (E2, E3 and E4), which are the gene products of three apo E alleles, e2, e3 and e4. Apo E lipoprotein plays an important role in the regulation of the lipid metabolism through its ability to bind to receptors. Depending on the genotypes apo E polymorphism is either protective or increases risk for atherosclerosis and coronary artery disease. The purpose of this study is to evaluate 1) the association between apo E allele and the development of coronary artery disease, 2) the association between apo E alleles and dyslipidemia in Korean males. METHODS: We studied 241 patients with angiographically verified coronary artery disease and 257 male subjects without evidence of coronary artery disease. Apo E genotyping was determined with the INNO-LiPA Apo E kit (Innogenetics, Belgium), which is based on reverse hybridization. RESULTS: There was a higher frequency of the apo e4 allele in subjects with coronary artery disease than in normal controls. The frequencies of apo E genotype were not significantly associated with apo e2 were associated with higher levels of triglyceride and lower LDL, and the subjects with apo e4 had lower levels of HDL cholesterol. CONCLUSION: ApoE polymorphism is a genetic marker for risk of the development of coronary artery disease and an important determinant of dyslipidemia.
Alleles ; Apolipoprotein E2 ; Apolipoprotein E4 ; Apolipoproteins E ; Apolipoproteins* ; Atherosclerosis ; Cholesterol, HDL ; Coronary Artery Disease* ; Coronary Vessels* ; Dyslipidemias ; Genetic Markers ; Genotype ; Humans ; Lipid Metabolism ; Lipoproteins ; Male* ; Protein Isoforms ; Triglycerides

Apolipoprotein E is a plasma protein that has an important role in transport and metabolism of lipids in serum as well as central nervous system. Among the 3 common alleles, the ε2 allele has the most stable structure followed by ε3 and ε4 in order. There is evidence for a deleterious role of ε4 allele by atherosclerosis and amyloid beta accumulation in brain and body. The presence and gene dose of ε4 allele are risk factors for late-onset Alzheimer's disease. Apolipoprotein E ε4 may have a role in the pathology of amyloid beta and tau and it has a strong relationship with the early onset of late-onset Alzheimer's disease. However, early-onset Alzheimer's disease has a weaker relationship with ε4 allele of apolipoprotein E.
Alleles ; Alzheimer Disease ; Amyloid ; Apolipoprotein E4* ; Apolipoproteins* ; Atherosclerosis ; Brain ; Central Nervous System ; Cognitive Aging* ; Metabolism ; Pathology ; Plasma ; Risk Factors*

PURPOSE: We studied to find out apo-E genotype polymorphism in minimal change nephrotic syndrome(MCNS) and IgA nephropathy(IgAN) and to determine the relationship between apo-E genotype and clinical course of MCNS. MATERIALS AND METHOD: 43 MCNS patients and 15 IgAN patients were examined for apo-E polymorphism. 50 healthy blood donors were examined for apo-E genotype as control. Genomic DNA was prepared from peripheral blood leukocytes according to standard procedures. RESULTS: As compared with control group, e4 allele frequency was significantly increased in MCNS (P<0.01). However, in IgAN e2 allele frequency, however, was 2.6 times higher than normal control (P<0.01). The frequency of e4 allele of frequent relapser group was 4.6 times higher than normal control and was 2 times higher than infrequent relapser group. CONCLUSION: We think that apo-E typing might be one of the parameters, which should be considered to predict the course of MCNS in children. MCNS with risky HLA profile and E4/4 genotype could indicate the need for a longer steroid dministration. And apo-E genotype needs to be considered for the evaluation of therapeutic responses to other drugs.
Alleles ; Apolipoprotein E4* ; Apolipoproteins E ; Apolipoproteins* ; Blood Donors ; Child ; DNA ; Gene Frequency ; Genotype* ; Humans ; Immunoglobulin A ; Leukocytes ; Nephrosis, Lipoid*

OBJECTIVE: Associations of vascular risk/disease or apolipoprotein E epsilon4(APOE4) with geriatric depression has been unclear at a population level. This study aimed to evaluate whether there would be interactions of vascular risk/disease and APOE4 on depression in a Korean elderly population. METHODS: 732 community residents aged 65 or over were assessed for depression(GMS), information on vascular risk/disease(reported stroke, transient ishemic attack, heart disease, hypertension, diabetes, smoking), examinations for vascular risk/disease(blood pressure, blood tests for glucose and lipid profiles, body size), APOE genotypes, demographic characteristics(age, gender, education), physical health, and cognitive function(MMSE). RESULTS: Previous stroke and lower level of high density lipoprotein(HDL) cholesterol were significantly associated with geriatric depression independent of demographic characteristics, physical illnesses, and cognitive function. These associations were statistically significant only in those with APOE4, although the interaction terms didn't reach to statistical significance. CONCLUSION: Associations between vascular risk/disease and geriatric depression might be more prominent in those with APOE4. However further research would be needed to clarify this issue.
Aged ; Apolipoprotein E4* ; Apolipoproteins E ; Apolipoproteins* ; Blood Pressure ; Cholesterol ; Depression* ; Genotype ; Glucose ; Heart Diseases ; Humans ; Hypertension ; Risk Factors* ; Stroke